The goal of this shared instrumentation proposal is to expand the capabilities of the Yale Positron Emission Tomography (PET) Center by the acquisition of a state-of-the-art PET/CT scanner for human research studies. PET imaging provides a non-invasive method to detect and examine biochemical processes and physiological functions in the living body. Through the use of specific radiolabeled molecules, state-of-the-art scanning equipment, and the techniques of tracer kinetic modeling, quantitative measurements of a wide range of physiological functions can be assessed in clinical and pre-clinical populations. PET has broad applications in the areas of oncology, cardiology, neurosciences, metabolic disorders, inflammation, and others. The goal of this proposal is to leverage the Yale PET Center's expertise in radiochemistry and quantitative PET imaging from our existing PET-only scanners and to expand the use of PET/CT in human research studies involving cardiovascular disease, diabetes, and oncology. Therefore, we have chosen the proposed PET/CT system with time-of-flight capabilities, high sensitivity and resolution, and excellent performance in terms of quantitative accuracy and count rate performance. When these PET instrumentation characteristics are combined with a CT scanner with excellent axial sampling and high speed, the system can provide ideal characteristics for PET/CT research studies of Yale investigators. The need for a combined PET/CT is self-evident for oncology research which requires simultaneous anatomical localization of tumor uptake. Work in diabetes requires combined PET/CT for pancreas measurements of 2 cell function and cardiovascular studies require combined PET/CT to correlate CT-based anatomical and functional measures with the physiological measurements from PET. The need for combined PET/CT will be of even greater importance in research studies using novel radiopharmaceuticals. The interpretation of the spatial localization of a new tracer, where normal uptake patterns are unknown, cannot be performed without high resolution anatomical data. In addition, the proposed high-end PET/CT will be of even greater utility when sophisticated multimodality image analysis techniques are employed, including image-based measurement of tracer input function and corrections for cardiac and respiratory motion artifacts. The proposed system will support NIH-funded investigators in the Departments of Cardiology, Diagnostic Radiology, Internal Medicine, Medical Oncology, Obstetrics and Gynecology, and Therapeutic Radiology. Enhanced utilization of novel radiopharmaceuticals and PET/CT imaging will lead to a better understanding of biochemical processes involved in cardiac disease, cancer, metabolic disorders, and others, which in turn will lead to the development of new, or improved treatment for these diseases. Together, these applications hold tremendous potential in improving the health of the general public. PUBLIC HEALTH RELEVANCE: This research project aims to provide state-of-the art imaging equipment for combined Positron Emission Tomography (PET) and CT research studies. PET/CT imaging is used to investigate and understand the biochemical and pathophysiological processes involved in cancers, metabolic diseases such as diabetes, and cardiovascular disease. Addition of a new PET/CT system will allow us to leverage the Yale PET Center's expertise in radiochemistry and quantitative PET imaging to support a wide range of clinical imaging research projects, which in turn will lead to the development of new disease treatments and new approaches for monitoring of disease progressions and treatment outcomes.